Involvement of the Fas (CD95) system in peripheral cell death and lymphoid organ development

Fas-mediated apoptosis is a form of cell death that operates through a Fas-Fas ligand (FasL) interaction. In this study we investigated the role of the Fas system during development of normal and Fas-mutated lymphocytes. Irradiated RAG2^–/– recipients were reconstituted with bone marrow cells from B6 and lpr mice (Fas defective) or from B6 and gld mice (FasL defective), and analyzed for long-term development. The results showed a primary role of the Fas system in peripheral cell death and thymic colonization. In the periphery, the interaction in vivo between Fas⁺ and Fas^– T cell populations indicated that cellular homeostasis was defective. Indeed, we observed a FasL-mediated cytotoxic effect on normal-derived T cells, explaining the dominance of lpr T cells in the mixed chimeras. The Fas mutation affected neither cell activation nor cell proliferation, as the effector (Fas^–) and target (Fas⁺) cells behaved similarly with regard to activation marker expression and cell cycle status. However, Fas^– T cells failed to seed the periphery and the thymus in the long term. We suggest that this could be due to the fact that FasL is involved in the structural organization of the lymphoid compartment.     

Characterizing the Dynamics of Postural Sway in Humans Using Smoothness and Regularity Measures

We investigate human postural sway velocity time series by computing two dynamical statistics quantifying the smoothness (the central tendency measure or CTM) and the regularity (the sample entropy or SampEn) of their underlying dynamics. The purpose of the study is to investigate the effect of aging and vision on the selected measures and to explore the nature of postural dynamics by performing surrogate data tests. A group of 14 young subjects was compared to a group of 11 older healthy subjects in two visual conditions: with eyes open (EO) and with eyes closed (EC). The results suggest that vision and age do not influence the two statistics of the velocity data in the same way. More specifically, the smoothness statistic is able to detect the aging effect. The regularity measure is sensitive to the visual feedback removal. In contrast with some findings in the literature, the results of the surrogate data tests indicate that the center of pressure velocity dynamics are stochastic and are not produced by a purely determinisitic behavior. Finally, we discuss some potential implications of our results in terms of postural control mechanisms.     

Development of a Kinetic Model for the Redox Reactions of Co2.4Ni0.6O4 and SiO2/Co2.4Ni0.6O4 Oxides for Thermochemical Energy Storage

One of the possible solutions for the transition of the actual energetic model is the use of thermal energy storage technologies. Among them, thermochemical energy storage based on redox reactions involving metal oxides is very promising due to its high energy density. This paper deals with the development of the kinetic study based on data extracted from the thermogravimetric analysis of a cobalt-nickel mixed oxide (Co_2.4Ni_0.6O₄) without and with the addition of SiO₂ particles to improve the cyclability. The results show that in the reduction reaction the activation energy is not affected by the addition of SiO₂ particles while in the oxidation reaction an increase in the activation energy is observed. The theoretical models fitting with the experimental data are different for each material in the reduction reaction. The mixed oxide is controlled by a nucleation and growth mechanism for conversion ratios higher than 0.5, while the added material is controlled by diffusion mechanisms. In the oxidation reaction, the two materials are controlled by a nucleation and growth mechanism for conversion ratios higher than 0.5.     

VIP Modulates IL-22R1 Expression and Prevents the Contribution of Rheumatoid Synovial Fibroblasts to IL-22-Mediated Joint Destruction

Rheumatoid arthritis (RA) and osteoarthritis are two rheumatic diseases whose progression is associated with a chronic synovitis. Fibroblast-like synoviocytes (FLS) have been shown to play a pivotal role in initiating and perpetuating inflammatory and destructive processes in the rheumatoid joint. Recently, the stimulating role of IL-22 has been reported on RA-FLS contribution to joint destruction by means of the increase of proliferation and matrix-metalloproteinase-1 (MMP-1) and alarmin S100A8/A9 production. Besides, mediators potentially present in inflamed joints have been shown to increase the expression of IL-22/IL-22R1 axis, amplifying the capacity of FLS to respond to IL-22 signalling. Since targeting cytokines that govern FLS activation would allow controlling their contribution to synovial inflammation, the present study was designed to analyze the potential immunoregulatory capacity of vasoactive intestinal peptide (VIP) to counterbalance IL-22 effects on FLS behavior. Our results showed that VIP is able to downregulate the augmented expression of IL-22 specific receptor in FLS subjected to a proinflammatory milieu. Moreover, this study revealed the ability of VIP to inhibit the IL-22 stimulatory effects on proliferation as well as on expression of both MMP-1 and alarmins in RA-FLS. The present findings reinforce the potential of this neuroimmunopeptide as a therapeutic agent in rheumatic diseases.     

Real‐time 3D target tracking in MRI guided focused ultrasound ablations in moving tissues

Magnetic resonance imaging‐guided high intensity focused ultrasound is a promising method for the noninvasive ablation of pathological tissue in abdominal organs such as liver and kidney. Due to the high perfusion rates of these organs, sustained sonications are required to achieve a sufficiently high temperature elevation to induce necrosis. However, the constant displacement of the target due to the respiratory cycle render continuous ablations challenging, since dynamic repositioning of the focal point is required. This study demonstrates subsecond 3D high intensity focused ultrasound‐beam steering under magnetic resonance‐guidance for the real‐time compensation of respiratory motion. The target is observed in 3D space by coupling rapid 2D magnetic resonance‐imaging with prospective slice tracking based on pencil‐beam navigator echoes. The magnetic resonance‐data is processed in real‐time by a computationally efficient reconstruction pipeline, which provides the position, the temperature and the thermal dose on‐the‐fly, and which feeds corrections into the high intensity focused ultrasound‐ablator. The effect of the residual update latency is reduced by using a 3D Kalman‐predictor for trajectory anticipation. The suggested method is characterized with phantom experiments and verified in vivo on porcine kidney. The results show that for update frequencies of more than 10 Hz and latencies of less then 114 msec, temperature elevations can be achieved, which are comparable to static experiments. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

Three-dimensional reconstructions for asymptomatic and cerebral palsy children's lower limbs using a biplanar X-ray system: A feasibility study

The aim of this study is to explore the feasibility of 3D subject-specific skeletal reconstructions of lower limb in children using stereoradiography, and to assess uncertainty of clinical and anatomical parameters for children with cerebral palsy and for healthy children. The stereoradiography technique, using the EOS^® system (Eos-imaging^®), is based on the acquisition of two simultaneous digital anteroposterior and lateral X-rays, from head to feet in standing position and at low radiation dose. This technique allows subject-specific skeletal 3D reconstructions. Five children with cerebral palsy (CP) and 5 typically developing children (TD) were included in the study. Two operators performed the lower limb reconstructions twice. Tridimensional reconstructions were feasible for children over the age of 5 years. The study of reproducibility of anatomical parameters defining skeletal alignment showed uncertainties under 3° for the neck shaft angle, the femoral mechanical angle, and for the femoral and tibial torsions. The maximum degree of uncertainty was obtained for the femoral tibial rotation (4° for healthy children and 3.5° for children with CP).     

Clinical study of 40 cases of incontinentia pigmenti

OBJECTIVE: To analyze the distribution of manifestations in a pediatric cohort and define guidelines for follow-up of incontinentia pigmenti (IP). DESIGN: Retrospective study of 47 children referred to the Department of Pediatric Dermatology with a diagnosis of IP between 1986 and 1999. SETTING: The private or institutional practice of participating dermatologists and pediatricians. MAIN OUTCOME MEASURES: Evaluation of IP clinical diagnosis using the Landy and Donnai criteria. RESULTS: Because hyperpigmentation following the Blaschko lines may be observed in several pigmented disorders, 7 patients were found misdiagnosed. During the neonatal period, erythema, vesicles, and hyperkeratotic le sions were rarely absent in the patients with IP. Ocular and neurological abnormalities were frequent (20% and 30%, respectively) but rarely severe (8% and 7.5%, respectively). CONCLUSIONS: Clinical diagnosis is the first main step for a correct phenotype/genotype correlation, which remains indispensable to better understand the pathological mechanisms of IP and develop new therapies. In doubtful cases, molecular analysis is helpful but characteristic histological features must be added as major criteria for IP diagnosis. Multidisciplinary follow-up is needed, particularly during the first year of life, to detect possible ophthalmologic and neurological complications. Neuroimaging ought to be performed in the case of abnormal neurological examination results or when vascular retinopathy is detected.